Lecture 2/3 - Pharmacokinetics Flashcards Preview

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Flashcards in Lecture 2/3 - Pharmacokinetics Deck (92):
1

What are the two methods of passive transport?

Channel mediated + Transporter mediated

2

What are three major components that go with carrier mediated transport?

Structure specific
Competition
Tmax

3

What are the two methods of carrier mediated methods?

Facilitated diffusion + Active transport

4

What is different about active transport compared to facilitated diffusion?

This method needs ATP in order to function

5

What is transcytosis?

Drug molecules + fluids are engulfed by the cell membrane and transported within the cell

6

What is the pH of most drugs given?

Weak acids or Weak bases

7

What is the most basic process that drugs undergo within the body ? (Hint: decides whether they are absorbed or not)

Ionization - phH dependent

8

What is the purpose of the Henderson-Hasselbach equation?

Tells you to what extent the drug is ionized within the body

9

What is A- form of the acid?

Ionized form

10

What is the HA form of the acid?

Unionized form

11

What is the B form of a base?

Unionized form

12

What is the BH+ form of a base?

Ionized form

13

What occurs to a weak acid within an acidic medium?

Less ionized
More lipid soluble
Rapidly absorbed

14

What occurs with a weak basic drug within basic medium?

Less ionized
Rapidly absorbed

15

What is an example, given in lecture, of an area with low pH?

The stomach (~2)

16

What is an example, given in lecture, of an area in the body with basic tendencies?

The intestines

17

What occurs when a basic drug is within an acid medium? What is this called?

Ionized and therefore will accumulate within the area. Known as ion trapping

18

What is the rule of thumb with both strong acids and bases within the body?

Always will be ionized within the body, so they are not lipid soluble meaning they will not undergo passive diffusion

19

What is the basic understanding of ion trapping?

Acids will be stuck in basic environments
Bases will be stuck in acidic environments

20

How do you make urine more acidic?

Ammonium chloride

21

How do you make urine more basic?

Sodium bicarbonate

22

What happens when you make urine more acidic?

Increase the elimination of bases via ion trapping

23

What happens when you make the urine more basic?

Increased elimination of acids, via ion trapping

24

What are the three types of active transport?

Uniport + Symport + Antiport

25

What is an example of a uniport given in lecture?

H+

26

What is an example of a symport given in lecture?

Glucose uptake

27

What is an example of an antiport given in the lecture?

Na/K ATPase

28

What is P-gp?

Permeability glycoprotein

29

What are two other names for P-gp?

MDRI
-- or --
ABCBI

30

What is the function of P-gp?

Utilizes ATP to pump out a WIDE variety of drugs across both extra/intracellular membranes

31

Where is P-gp located?

Pretty much everywhere, important to know it is found in the BBB

32

What is absorption in regards to a drug?

Process where drug gains entry into body fluids (normally blood) and moves throughout the organism

33

What are seven things that tend to affect absorption?

Solubilty + Dissolution + Concentration + Blood flow + SA + pH + Contact time

34

What is bioavailability?

Amount of active drug available at the site of action

35

What four things play a role in bioavailability?

Decomposition of drug in intestines
Degree of absorption
Metabolism in wall of gut or liver
Transport of drug back into lumen via P-gp

36

What is the first pass effect?

Initial metabolism of drug, occurs through wall of gut or liver

37

What is the most common method by which a drug is administered?

Per os (by mouth)

38

What is the downside to a slow release formulation?

Absorption is irregular and erratic

39

What are the disadvantages to per os method of drug administration?

Destruction of drug due to low pH
Gastric emptying time
binding to food
Metabolism by microbes
Exposed to liver

40

What does the process of drug distribution entail?

Movement of drug from systemic circulation to organs/tissues

41

Where are the three popular sites in the body that drugs accumulate?

Fat + Tissues + Bone

42

What affects do storage depots have on the drugs metabolism?

decrease plasma levels
-- and --
prolong half lives

43

Where are the five sites of exclusion?

CSF + Ocular + Endolymph + Fetal + Pleural

44

What two components help define volume of distribution?

Plasma concentration of drug at time zero
Intravenous dose

45

What is the standard plasma size of a 70kg dog?

3L

46

What is the standard EC compartment size in a 70kg dog?

12 L

47

What is the standard Total body water compartment in a 70kg dog?

41 L

48

What does a large Vd mean?

The drug is either distributed extensively or has bound extensively to peripheral tissues

49

What does a very low Vd mean?

Drug is mostly present in the plasma, very high plasma protein binding

50

What are the characteristics of most active drugs?

Lipid soluble
Unionized at physiological pH
Strongly bound to plasma proteins
Not readily excreted by kidneys
Remain in body for long periods of time

51

What is the most basic thing that happens in phase II reactions?

Conjugation

52

What is the most basic way to describe what occurs in a phase I reaction?

Modification of the molecule

53

What commonly occurs within the phase I reaction?

Lipid soluble parent compound converted to more polar metabolites
Most commonly these are inactive and therefore excreted

54

What does the phase I reaction do to the chemical structure of most drugs?

introduce or unmask functional groups (-OH, SH, NH2, etc)

55

What are the two types of phase I reactions?

Non-microsomal + Microsomal

56

Is phase I specific to certain compounds?

No, enzymes are focused on specific groups/bonds

57

What are five enzymes that are examples of nonmicrosomal metabolism in phase I?

Esterases/amidases
Monoamine oxiidases
Alcohol/aldehyde dehydrogenases

58

What is a Phase I microsomal reaction?

Drug oxidation via P450 (and other biological variations)

59

How do microsomal reactions differ from non-microsomal Phase I reactions?

Induction + Inhibition can occur

60

How is Phase II reactions similar to Phase I?

Not compound specific

61

What type of reactions are Phase II reactions?

Synthetic

62

What are the results of Phase II reactions?

Larger molecular weight
Increased polarity
Decreased biological activity

63

What is the only microsomal Phase II reaction?

Glucuronidation (therefore it is inducible)

64

What are the five major types of phase II reactions?

Glucuronidation
Acetylation
Glutathione conjugation
Glycine conjugation
Sulfation

65

What is the endogenous reactant in glucuronidation?

UDP glucuronic acid

66

What is the transferase/location for glucuronidation?

UDP-glucuronosyltransferase
Microsomes

67

What is the endogenous reactant for acetylation?

Acetyl-Coa

68

What is the transferase/location for Actylation?

N-acetyltransferase
Cytosol

69

What is the endogenous reactant for glutathione conjugation?

Glutathione (GSH)

70

What is the transferase/location for glutathione conjugation?

GSH-S-transferase
Cytosol - Microsomes

71

What is the endogenous reactant for glycine conjugation?

Glycine

72

What is the transferase/location for glycine conjugation?

Acyl-CoA glycinetransferase
Mitochondria

73

What is the endogenous reactant for sulfation?

Phosphoadenosyl phosphosulfate

74

What is the transferase/location for sulfation?

Sulfotransferase (cytosol)

75

What is the path for renal excretion of drugs and their metabolites?

Glomerular filtration
Active tubular secretion or reabsorption
Passive diffusion across tubular epithelium

76

What does clearance pertain to?

The ability of the body to remove the drug

77

What two things does clearance relate?

Rate of drug elimination + Plasma concentration

78

What are the two phases of the two-compartment model?

Distribution + Elimination

79

Why do you see initial rapid changes in the two compartment model graph?

Shows the time it takes for the drug to reach an equilibrium between the central compartment and the plasma space

80

What order is the elimination phase in the two compartment model?

First-order, we know this because of it's linear pattern

81

What is used to get the elimination rate in the two compartment model?

K - aka the slope of the linear portion of the graph

82

What on the graph of the two compartment model tells you Co? What does that mean?

Where the linear line intercepts the Y-axis, this gives you the plasma concentration of the drug at time zero.

83

What is the most common order of elimination?

First-order

84

What does first order elimination mean?

constant proportion of the drug is eliminated per unit time

85

Why do you get first order elimination?

Elimination system is not saturated by the drug

86

What does half life mean?

Time required to change amount of drug in body by one-half

87

What are you assuming when you determine 1/2 life?

Body is single compartment
Size = Vd
Drug is distributed equally
Drug in plasma is in equillibrium w/ total volume

88

What is zero order elimination?

The elimination system becomes saturated after a high dose of the drug, meaning only a constant amount can be eliminated per unit time

89

What needs to be done to reach steady state with repeated administration?

Interval of time it takes to reach SS is equal to five half lives

90

What is a loading dose?

Done for immediate therapeutic concentration

91

What follows a loading dose?

Maintenance dose

92

What are the three stages of Pharmacokinetics?

Absorption + Distribution + Elimination